This application requests resources to support 42 trainees per year through the Medical Scientist Training Program (MSTP) at the University of California, San Francisco (UCSF). The MSTP has the goal of training the next generation of physician-investigators by offering a rigorous, integrated, and supportive educational experience leading to both M.D. and Ph.D. degrees. The UCSF MSTP offers the combination of an outstanding public medical school with an innovative curriculum, committed and renowned faculty, and a collection of premier graduate training programs. The program is currently in its 33rd year of continuous NIH support. From its inception, the guiding principles have been: (1) selecting outstanding students who are committed to careers as physician-investigators and who have the academic ability and interpersonal skills to excel in medicine and science; (2) offering the best possible training leading to combined M.D. and Ph.D. degrees without compromising the quality of training for either degree; and, (3) actively engaging the UCSF School of Medicine (SOM) and Graduate Programs to optimize the training path of each student and to encourage efficient completion of both degrees. During the current period of T32 support, our MSTP has continued to attract and train exceptional students who have a remarkable record of success. The leaders of the SOM have demonstrated an extraordinary level of commitment to the program, which has increased in size from 67 to 87 trainees. New activities to enhance and optimize the training of students have been added during the current period of support. Our trainees have formed a strong community that has engaged the faculty to enhance the training environment at UCSF. The achievements of our students and their subsequent track records underscore the value of this combined degree program. This application is directly relevant to the mission of the NIGMS and NIH as it requests funds to support mentored career development for the next generation of physician-scientists. This MSTP represents an investment in the future of our nation's health as the researchers who are trained through this award will be optimally prepared to harness discovery-based research strategies to attack urgent problems in human health with the goal of developing and implement innovative new treatments.